Indiana cultivates approximately 7000 acres of watermelons (Citrullus lanatus) every year, with the majority of production concentrated in southern Indiana, thus making this region a key area for watermelon production in the United States. Diverse irrigation and fertilization practices are used for watermelon production in the region, yet their effects on production outcomes remain poorly understood. To address this knowledge gap, this study investigated the impact of existing practices on watermelon yield to optimize irrigation and fertilization practices for improved production. The experiment was conducted at the Southwest Purdue Agricultural Center, Vincennes, IN, USA, during the 2022 and 2023 watermelon seasons. The following four treatments were applied: high irrigation, low irrigation, no irrigation, and fertigation. The fertigation treatment received the same water application as the high irrigation treatment, but with frequent fertilizer application with irrigation; however, fertilizers were applied before planting in the high, low, and no irrigation treatments. Although soil moisture levels at the different depths varied notably among treatments, no significant differences in yield by weight were observed. The minimal impact of irrigation on watermelon yield suggested that sufficient water is stored in the soil to prevent yield-reducing stress during dry periods. However, the high irrigation and fertilization treatments produced more fruit than the low irrigation and no irrigation treatments. The dry periods during both years coincided with the watermelon fruit-setting stages, potentially contributing to the lower fruit set in the low irrigation and no irrigation treatments. Fertigation showed a higher early yield in 2022 than that of the other treatments. An analysis of soil and tissue nitrogen levels indicated that solely applying nitrogen before planting could lead to excessive soil nitrogen during vegetative growth. This excess nitrogen might delay flowering and harvest. This project offers insights into enhancing irrigation and fertilization practices for watermelon production in southern Indiana, provides recommendations, and discusses future research directions.